title: Diet-induced obesity increases melanoma progression: involvement of Cav-1 and FASN.
abstract: Recent population-based epidemiological studies strongly hint towards a link between obesity and its occurrence as well as progression of several cancers including melanoma. Although effects of obesity on breast, colon and liver cancers have been extensively investigated, the links between obesity and melanoma remain largely unexplored. Present study aimed to understand the effect of high fat diet-induced weight gain on susceptibility of C57BL/6J mice to melanoma. For this, mice routinely were fed on high fat diet for 6 months (HFD mice). Subsequently, mouse melanoma cells were injected subcutaneously in control as well as HFD mice and followed for tumor initiation and progression. We provide strong evidence that diet-induced obesity leads to increased melanoma progression in male C57BL/6J mice. We observed that increased melanoma progression is associated with enhanced Cav-1 and FASN expression in tumors from HFD mice. Cav-1 and FASN are co-ordinately regulated and Cav-1 interacts with FASN in melanoma cells. Enhanced levels of Cav-1, FASN and pAkt control melanoma cell proliferation. Our study establishes a causative relationship between diet-induced obesity and melanoma progression as well as demonstrates that obesity affects important tumorigenic pathways in melanoma.
authors.affiliation: National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune, India.
authors.forename: Vimal
authors.initials: V
authors.lastname: Pandey
authors.forename: Maleppillil Vavachan
authors.initials: MV
authors.lastname: Vijayakumar
authors.forename: Amrendra Kumar
authors.initials: AK
authors.lastname: Ajay
authors.forename: Parmanand
authors.initials: P
authors.lastname: Malvi
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Bhat
mesh_terms: D054392:Adipokines / Q000097:blood; D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059305:Diet, High-Fat; D018450:Disease Progression; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D008055:Lipids / Q000097:blood; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011485:Protein Binding; D015430:Weight Gain
chemical_list: D054392:Adipokines; D051242:Caveolin 1; D008055:Lipids; D064429:Fatty Acid Synthases; D051058:Oncogene Protein v-akt